Dromi N, Avihoo A, Barash D
Department of Computer Science, Ben-Gurion University, Beer-Sheva 84105, Israel.
J Biomol Struct Dyn. 2008 Aug;26(1):147-62. doi: 10.1080/07391102.2008.10507231.
The process of designing novel RNA sequences by inverse RNA folding, available in tools such as RNAinverse and InfoRNA, can be thought of as a reconstruction of RNAs from secondary structure. In this reconstruction problem, no physical measures are considered as additional constraints that are independent of structure, aside of the goal to reach the same secondary structure as the input using energy minimization methods. An extension of the reconstruction problem can be formulated since in many cases of natural RNAs, it is desired to analyze the sequence and structure of RNA molecules using various physical quantifiable measures. In prior works that used secondary structure predictions, it has been shown that natural RNAs differ significantly from random RNAs in some of these measures. Thus, we relax the problem of reconstructing RNAs from secondary structure into reconstructing RNAs from shapes, and in turn incorporate physical quantities as constraints. This allows for the design of novel RNA sequences by inverse folding while considering various physical quantities of interest such as thermodynamic stability, mutational robustness, and linguistic complexity. At the expense of altering the number of nucleotides in stems and loops, for example, physical measures can be taken into account. We use evolutionary computation for the new reconstruction problem and illustrate the procedure on various natural RNAs.
通过反向RNA折叠设计新型RNA序列的过程（如RNAinverse和InfoRNA等工具中可用）可被视为从二级结构重建RNA。在这个重建问题中，除了使用能量最小化方法达到与输入相同的二级结构这一目标外，没有将任何物理量视为独立于结构的额外约束。由于在许多天然RNA的情况下，希望使用各种物理可量化度量来分析RNA分子的序列和结构，因此可以提出重建问题的扩展。在先前使用二级结构预测的工作中，已经表明天然RNA在其中一些度量上与随机RNA有显著差异。因此，我们将从二级结构重建RNA的问题放宽为从形状重建RNA，进而将物理量纳入约束条件。这使得在考虑诸如热力学稳定性、突变鲁棒性和语言复杂性等各种感兴趣的物理量的同时，能够通过反向折叠设计新型RNA序列。例如，以改变茎和环中核苷酸数量为代价，可以考虑物理量。我们将进化计算用于新的重建问题，并在各种天然RNA上说明了该过程。
